丹参酸A治疗心肌梗死的药理靶点及作用机制的网络药理学分析
Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction.
作者信息
Huang Qing, Zhang Chao, Tang Shaoyong, Wu Xiaoyan, Peng Xiong
机构信息
Department of Cardiology, Wuhan Fourth Hospital, Wuhan, Hubei, China.
Heart Function Testing Center of Cardiovascular Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
出版信息
Evid Based Complement Alternat Med. 2022 Oct 5;2022:8954035. doi: 10.1155/2022/8954035. eCollection 2022.
OBJECTIVE
Salvianolic acid A, a natural polyphenolic ingredient extracted from traditional Chinese medicine, possesses an excellent pharmacological activity against cardiovascular diseases. Herein, therapeutic mechanisms of salvianolic acid A in myocardial infarction were explored through systematic and comprehensive network pharmacology analyses.
METHODS
The chemical structure of salvianolic acid A was retrieved from PubChem database. Targets of salvianolic acid A were estimated through SwissTargetPrediction, HERB, and TargetNet databases. Additionally, by GeneCards, OMIM, DisGeNET, and TTD online tools, myocardial infarction-relevant targets were predicted. Following intersection, therapeutic targets were determined. The interaction of their products was evaluated with STRING database, and hub therapeutic targets were selected. GO and KEGG enrichment analyses of therapeutic targets were then implemented. H9C2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic myocardial infarction and administrated with salvianolic acid A. Cellular proliferation was assayed via CCK-8 assay, and hub therapeutic targets were verified with RT-qPCR.
RESULTS
In total, 120 therapeutic targets of salvianolic acid A in myocardial infarction were identified. There were close interactions between their products. Ten hub therapeutic targets were determined, covering SRC, CTNNB1, PIK3CA, AKT1, RELA, EGFR, FYN, ITGB1, MAPK8, and NFKB1. Therapeutic targets were significantly correlated to myocardial infarction-relevant pathways, especially PI3K-Akt signaling pathway. Salvianolic acid A administration remarkably ameliorated the viability of OGD/R-induced H9C2 cells, and altered the expression of hub therapeutic targets.
CONCLUSION
Our work uncovers therapeutic mechanisms of salvianolic acid A for the treatment of myocardial infarction, providing a new insight into further research on salvianolic acid A.
目的
丹酚酸A是从中药中提取的一种天然多酚成分，对心血管疾病具有优异的药理活性。在此，通过系统和全面的网络药理学分析探索丹酚酸A在心肌梗死中的治疗机制。
方法
从PubChem数据库检索丹酚酸A的化学结构。通过SwissTargetPrediction、HERB和TargetNet数据库评估丹酚酸A的靶点。此外，通过GeneCards、OMIM、DisGeNET和TTD在线工具预测心肌梗死相关靶点。经过交集分析，确定治疗靶点。用STRING数据库评估其产物的相互作用，并选择核心治疗靶点。然后对治疗靶点进行GO和KEGG富集分析。将H9C2细胞暴露于氧糖剥夺/复氧（OGD/R）以模拟心肌梗死，并给予丹酚酸A。通过CCK-8法检测细胞增殖，并用RT-qPCR验证核心治疗靶点。
结果
共鉴定出丹酚酸A在心肌梗死中的120个治疗靶点。它们的产物之间存在密切相互作用。确定了10个核心治疗靶点，包括SRC、CTNNB1、PIK3CA、AKT1、RELA、EGFR、FYN、ITGB1、MAPK8和NFKB1。治疗靶点与心肌梗死相关通路显著相关，尤其是PI3K-Akt信号通路。给予丹酚酸A可显著改善OGD/R诱导的H9C2细胞活力，并改变核心治疗靶点的表达。
结论
我们的工作揭示了丹酚酸A治疗心肌梗死的机制，为丹酚酸A的进一步研究提供了新的见解。
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